Physiology of pain 2 Flashcards
What is meant by chronic pain?
greater than 3 months
What is meant by acute pain?
Less than 3 months
Give examples of acute pain
Following surgery
Musculoskeletal injury
Burn
Describe inflammatory pain
Due to tissue injury or inflammation
What is peripheral sensitisation?
Leads to pain hypersensitivity (hyperalgesia)
Reduction in the threshold of TRPV1 channels (by bradykinin, nerve growth factor)
Reduction in threshold in Na+ channels (prostaglandins)
What are the sites of treatment for acute pain?
PNS (site of injury)
CNS
Both
Describe local anaesthetics and how they work
Lidocaine or lignocaine
Topically applied to the skin
Sodium channel blockers - prevent nociceptor firing
Describe capsaicin treatment
Component of chilli peppers
TRPV1 channel agonist
Repeated uses reduce nociceptor firing
Mechanism of action - depletes substance P causes peripheral terminals to die back
Describe nonsteroidal antiinflammatory drugs and their mechanism of action
Eg. aspirin and ibuprofen
Reduces the inflammatory response by inhibiting prostaglandin synthesis - prevents peripheral sensitisation
Cyclooxygenase inhibitor - prostaglandin synthesis reduced - prevents decrease in Na+ channel threshold
Describe the action of paracetamol/acetaminophen
Not NSAID
Mechanism of action:- Inhibits cyclooxygenase (COX) enzymes (But does not reduce inflammation)
- Acts on descending serotonergic pathways
Describe the action of opiods
Eg. morphine, codeine, tramadol
Most effective pain relief but numerous side effects
Mechanism of action : Agonist of the endogenous opioid system
- Multiple sites of action -Brainstem (Disinhibition)
-Spinal cord
-Peripheral (inhibit channels on nociceptors)
What is gate control theory?
Modulation of pain at the spinal cord level
Pain evoked by nociceptors can be reduced by simultaneous activation of low threshold mechanoreceptors (Aβ fibres)
Simply rubbing/blowing on the painful area can reduce the pain sensation
Stimulation of Ab-fibres in vicinity of injury activates interneurons in dorsal horn, which inhibit spinothalamic neurons
C fibres inhibit inhibitory interneurons – opens gate
Aβ fibres activate inhibitory interneurons – closes gate
What is chronic pain?
Pain persists (>3 months)
Common - affects 20-50% OF THE POPULATION
E.g. Chronic back pain, cancer, carpal tunnel syndrome, arthritis, fibromyalgia, diabetes, migraine, post-surgery, multiple sclerosis, trigeminal neuralgia, phantom limb pain…
What types of chronic pain exists?
Inflammatory - persistent tissue inflammation
Neuropathic - Due to injury to nervous system
What are the symptoms of neuropathic pain?
Burning Constant Stabbing Aching Electricity/shocking Spontaneous Hypersensitivity
What are the main peripheral mechanisms of neuropathic pain?
Peripheral sensitization
Spontaneous firing of nociceptors
Describe the spontaneous firing of nociceptors
Following a peripheral nerve injury, there is an increase in axonal firing at the injury site, due to:Accumulation of ion channels at regenerating tip of axon
- Responsible for spontaneous pain
- Underlies central neuropathic pain mechanisms
List the main central mechanisms of neuropathic pain
Main central mechanisms:
- Central sensitization
– within spinal cord - Changes in activation patterns/cortical remapping
– within brain
Describe central sensitisation
Increase in the responsiveness of nociceptive neurons within the central nervous system
- Normal inputs begin to produce abnormal responses
Due to the reduced threshold for activation of 2nd order neurons (similar to LTP)
Describe reduced threshold for activation of second order neurons
Constant firing of axons from the periphery
Sustained release of glutamate
Prolonged depolarisation of the postsynaptic membrane
Massive influx of Ca2+ through NMDA receptors
Activation of kinase
Phosphorylation of NMDA/AMPA receptors and channel protein synthesis
Alters kinetics of channels and causes insertion of more channels
Describe the central hyperalgesia mechanism
Following central sensitization:
Activation of nociceptors results in amplified spinal cord activation
Describe the central allodynia mechanism
Non-noxious Aβ fibres also synapse onto 2nd order spinothalamic neurons - Normally these are non-functional
Following central sensitization:
Non-noxious afferents activate sensitized 2nd order neurons
What is the problem with central changes?
Not easily reversible
Describe chronic pain treatments
Difficult to treat
Acute pain treatments often do not work
Good individual patient management is critical
Important to manage primary conditions and associated symptoms - Depression, sleep disturbance, fatigue
List some current treatments for chronic pain
Drugs: - Tricyclic antidepressants - Anticonvulsants - NMDA antagonists (All have analgesic properties)
Physiotherapy – e.g. manipulation of tissues, pacing
Psychological therapies – e.g. cognitive behavioral therapy
Surgery – e.g. spinal cord stimulator
Describe tricyclic antidepressants and their mode of action
E.g. Amitriptyline
Mechanism of action:
- Unclear - Act on descending inhibitory pathways - Inhibits reuptake of serotonin (and noradrenalin)
Describe anticonvulsants and their mechanism of action
Pregabalin / gabapentin, carbamazepine
Mechanism of action:
- Unclear - Act in spinal cord to reduce excitability - Blocks calcium (pregabalin/gabapentin) and sodium (carbomazepine) channels
Pregabalin/gabapentin do not act on GABAergic interneurons
- Blocks presynaptic voltage-gated Ca2+ channels - Prevent release of glutamate from nociceptors
What are NMDA antagonists and their mode of action?
Ketamine
Mechanism of action:
- NMDA receptor antagonist (reduces glutamate influx) - Prevents depolarization of second order neuron - Adverse side effects (hallucinations/bad dreams)
What are the NICE guidelines on the treatment of neuropathic pain
First-line of treatment:
- Amitriptyline or pregabalin
Second-line of treatment:
- Switch drugs or combine
Third-line of treatment:
- Refer patient to a specialist pain service and consider oral tramadol (opioid) or in combination with the second-line treatment consider topical lidocaine
Describe the placebo effect of neuropathic pain
Placebo analgesia has been demonstrated (in well controlled studies) for the treatment of neuropathic pain
- Due to activation of descending inhibitory pathways
List some complementary alternative therapies
Acupuncture, massage therapy, homeopathy, herbal medicine, hypnosis
